Interactions of Apomorphine and a Novel Neuroleptic Dibenzodioxazocine Derivative, as Evidenced by Changes of Somato-autonomic Reflexes and Spontaneous Sympathetic Activity in Cats

Abstract

Abstract The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg−1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0·2 mg kg−1 i.v.) at low frequencies of stimuli (2–8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1·5 mg kg−1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1·5 mg kg −1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18·5 mg kg−1): after EGYT-2509, higher doses of apomorphine (0·7 vs 0·2 mg kg−1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8·5 vs 18·5 mg kg−1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg−1 i.p., respectively), apomorphine (0·2 mg kg−1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve. EGYT-2509 (<1 mg kg−1) and chlorpromazine (0·2-0·5 mg kg−1) failed to antagonize the apomorphine-induced inhibition. Haloperidol (0·4 mg kg−1), however, restored the renal nerve activity. All three compounds, EGYT-2509, chlorpromazine and haloperidol, themselves, inhibited the sympathetic discharges. The results indicate that EGYT-2509, in addition to its potent anti-apomorphine activity, possesses some apomorphine-like features, too.